Over 2 million Americans are hospitalized annually with a myocardial infarction (MI) or unstable angina pectoris, two acute, potentially fatal manifestations of coronary heart disease (CHD) that are responsible for substantial morbidity, mortality, and health care costs. Smoking cessation is highly cost-effective and universally recommended for the approximately 20 percent of these patients who smoke. Hospitalization for acute CHD is an excellent time to initiate smoking cessation because it requires temporary tobacco abstinence at the same time that illness increases smokers' motivation to quit. However, at least 40 percent of smokers fail to quit even with the most effective current treatment, cognitive-behavioral counseling that begins in the hospital and continues after discharge. More powerful intervention strategies are clearly needed. Adding pharmacotherapy to counseling, which is standard practice in outpatients, is a new approach that has not been tested in this setting. Concern about the safety of nicotine replacement in MI patients limits its use. A non-nicotine antidepressant, sustained-release (SR) bupropion (Zyban, Wellbutrin SR), has demonstrated efficacy for smoking cessation and was recently FDA- approved for this use. Bupropion appears to be safe in cardiac patients and may have the additional benefit of preventing post-MI depression, an independent predictor of mortality. We propose to test the efficacy and safety of this novel treatment, bupropion SR, for smoking cessation in adult smokers hospitalized with acute CHD. We have designed a randomized, double-blind, placebo-controlled trial to determine whether bupropion SR, initiated in the hospital and continued for 12 weeks, is effective and safe when added to a previously-tested nurse-delivered cognitive-behavioral smoking counseling intervention that begins in the hospital and continues by telephone contact after discharge. Outcomes will be assessed at hospital discharge and 1, 3, and 12 months after the start of treatment. The primary outcome measure is biochemically-confirmed 7-day point prevalence tobacco abstinence at 1 year follow-up. Secondary objectives are to test whether bupropion SR delays the time to smoking relapse; increases the smoking cessation rate at the end of treatment (3-months); and reduces CHD morbidity and depressive symptoms and improves health-related quality of life over 1 year. If found to be safe and effective, bupropion SR could become a standard part of "secondary prevention" therapy for smokers with acute CHD, a large, high-risk, high-cost patient group.